Estradiol derivatives bearing sulfur-containing substituents at the 11β or 7α positions: Versatile reagents for the preparation of estrogen conjugates

Estradiol derivatives bearing HS-, HSCH₂-, HSCH ₂CH₂-, MeS-, MeSCH₂-, MeSCH₂CH ₂-, or PhCH₂SCH₂CH₂-groups at the 11β position or an HS-group at the 7α position have been synthesized, and their binding affinity to the estrogen receptor (ER) determined. Nearly all of these substituted estrogens retain high binding affinity, and at the 11β position, the sulfur atom has an effect on ER binding that is similar to that of a carbon atom. These thiol derivatives are promising intermediates for the preparation of a variety of estradiol conjugates. The methyl sulfides, in particular, might potentially be developed as ¹¹C-labeled agents for imaging ER-positive tumors by positron emission tomography.